Method of controlling immune cells

ABSTRACT

A method for regulating immune cells includes applying a stimulus to a specific area to be stimulated at a body surface by a stimulus applying apparatus so as to bring an increase rate of a blood flow to 60% or more, preferably, 100% or more. The blood flow is measured by a laser Doppler tissue blood flow meter attached to a central part of an inner side of a wrist joint. The regulating and balancing these T cell groups finely is essential to maintain the immune system of human beings and increase in blood flow volume by thermal therapy enables a regulatory T cell to regulate and balance the immune cells.

CROSS-REFERENCES TO RELATED APPLICATION

This application is a CIP of application Ser. No. 13/551,730, filed Jul.18, 2012, which claims priority to U.S. Provisional Patent ApplicationSer. No. 61/508,883 filed Jul. 18, 2011, U.S. Provisional PatentApplication Ser. No. 61/526,089 filed Aug. 22, 2011, and U.S.Provisional Patent Application Ser. No. 61/635,359 filed Apr. 19, 2012,the contents of which are incorporated herein by reference in theirentireties. This application also claims priority to U.S. ProvisionalPatent Application Ser. No. 62/035,103 filed Aug. 8, 2014, the contentsof which are incorporated herein by reference in their entireties. Thisapplication has related application Ser. No. 14/703,021, filed May 4,2015, which is a CIP of the same parent, application Ser. No.13/551,730, filed Jul. 18, 2012. The contents of application Ser. No.14/703,021, filed May 4, 2015 are incorporated herein by reference intheir entireties

BACKGROUND

1. Technical Field

The present invention relates to a stimulus method in which stress isreleased in order to improve lifestyle-related diseases such as thediabetes, obesity and high blood pressure resulting from the stress, byactivating a peripheral circulatory function and an autonomic nervousfunction through a stimulus to specific parts of a body surface by anacupuncture needle(s) or heating etc. thereby releasing the stress, anda stress-free medical treatment method based on the stimulus method.

2. Related Art

U.S. Pat. No. 5,950,635 discloses a point surface stimulus methodaccording to a specific acupuncture treatment for reducing anxiousness,for example, stress. The patent discloses that LR3, HT3, and PC6 arespecified as stimulus points of patients. Electrodes are brought intocontact with these three stimulus points, respectively, thereby passingcurrent through the electrode. Here, the LR3 is located on the top ofthe foot, at 2 cm proximal to the margin of the first and second toes.The HT3 is located on the inside of each elbow, midway between themedial end of an elbow crease and the medial epi-condyle of the humeruswhen the elbow is fully flexed. The PC6 is located on each wrist, 2 cmproximal to the midpoint of the wrist crease between the tendons of thepalmaris longus and the flexor carpi radialis muscle. In the patent, aP1 potential is focused on with respect to at least one subcorticalsource, specifically in the pedunculopontine nucles (PPN), thechlinergic arm of the reticular activating system. That is, the patentdiscloses that when the above-mentioned stimulus points (LR3, HT3, andPC6) are stimulated with needles, the P1 potential decreases andanxiousness is reduced. In addition, other than the stimulus points LR3,HT3, and PC6, no stimulus points to be stimulated with the needles aredisclosed. However, the patent discloses that, focusing onpedunculopontine nucles (PPN), anxiousness is reduced due to a decreaseof the P1 potential. However, it does not discloses that due toreduction of anxiousness, it is possible to achieve effects, such asnormalization of blood pressure, degression of stress, rise in bodytemperature, degression of neutral fat, degression of cholesterol, andan improvement of a blood sugar level due to relief of insulinresistance.

SUMMARY

By earnest research work, the present inventor found out a specific areato be stimulated, at which diabetes resulting from stress, andlifestyle-related diseases such as obesity and high blood pressure canbe improved by making psychological stress free by a stimulus throughacupuncture needles or heating to specific area to be stimulated of abody surface.

It is an object of the present invention to provide a body surfacestimulus method for releasing psychological stress, in which stress ismade free by activating a peripheral circulatory function and anautonomic nervous function by applying acupuncture needles to specificarea to be stimulated of a body surface, or a stimulus based on heatingetc., so that a symptom of diabetes resulting from the stress and asymptom of lifestyle-related disease such as obesity and high bloodpressure may be improved.

It is another object of the present invention to provide a stress-freetreatment using the body surface stimulus method for releasing thepsychological stress.

According to the present invention, since a specific area to bestimulated of a body surface by acupuncture needles or heating etc.affects a homeostatic function (nerve, immunity, and endocrine system)though a peripheral circulatory function and autonomic nerves, it ispossible to obtain effects, such as a normalization of blood pressure, areduction of stress, a rise in body temperature, a degression of neutralfat, a degression of cholesterol, and an improvement of a blood sugarlevel due to relief of insulin resistance.

In the present invention, stimuli are, non-simultaneously andindependently from each other, applied to at least one area selectedaccording to the condition of disease, thereby achieving a reduction ofpsychological stress, a rise in core body temperature, a reduction ofneutral fat, a reduction of cholesterol, an improvement of a blood sugarlevel by relief of insulin resistance, and suppression ofarteriosclerosis.

In the present invention, a stimulation of a thermal stimulus pattern,which is formed by controlling an electric type heating apparatus, isnon-simultaneously and independently applied to at least one areasselected according to the condition of disease, thereby achieving areduction of psychological stress, a rise in core body temperature, areduction of neutral fat, a reduction of cholesterol, an improvement ofa blood sugar level by relief of insulin resistance, and suppression ofarteriosclerosis.

In one embodiment, a stimulus treatment method for providing medicaltreatment by applying a stimulus to a specific area to be stimulated ata body surface by a stimulus applying apparatus so as to bring anincrease rate of blood flow to 60% or more, preferably, 100% or more,wherein the blood flow is measured by a laser Doppler tissue blood flowmeter attached to a central part of an inner side of a wrist joint.

The specific area may be at least one area selected from a group of osmetatarsale primam 1 and 2 interosseous, os metatarsale primam 2 and 3interosseous, and part that intersects the perpendicular line of themedial malleolus on an extension line of the medial margin on osmetatarsale primam 1 and 2 in foot sole of right and left.

The specific area may be an area of a near glandula thyreoidea.

The specific area may be an area between the outer skin and a horizontalline of the inside boundary part of a hallux distal phalanx bottom and aproximal phalanx bone head in foot sole of right and left.

The stimulus may be non-simultaneously and independently applied to atleast one area selected according to a condition of disease.

The stimulus applying apparatus may be a heat stimulus applyingapparatus, and the heat stimulus applying apparatus forms a warmtemperature stimulus pattern, wherein the stimulus pattern is made up ofa thermal stimulus waveform and an interval, and the thermal stimuluswaveform includes a heating waveform obtained by raising temperature toa peak temperature, 50±5 degrees Celsius by heating, and a heat releasewaveform formed by stopping the heating when the peak temperature isreached.

The stimulus may be selected from an acupuncture needle stimulus, a warmtemperature stimulus, an optical stimulus, a magnetic stimulus, and anultrasonic stimulus. A stress-free treatment method includes thestimulus method according to any one of the methods described above. Anstimulus evaluation method includes a stimulus method according to anyone of the methods described above, in which the increase rate of theblood flow is used as an indicator of the stimulus evaluation.

It is yet another object of the present invention to provide a method ofregulating immune cells. One embodiment of the method for regulatingimmune cells includes applying a stimulus to a specific area to bestimulated at a body surface by a stimulus applying apparatus so as tobring an increase rate of a blood flow to 60% or more, preferably, 100%or more, wherein the blood flow is measured by a laser Doppler tissueblood flow meter attached to a central part of an inner side of a wristjoint, and wherein regulating and balancing these T cell groups finelyis essential to maintain the immune system of human beings and increasein blood flow volume by thermal therapy enables a regulatory T cell toregulate and balance the immune cells.

In another embodiment, a method for regulating immune cells includescontacting a thermal application terminal with at least two differentbody sites of a body surface to apply a thermal stimulus to the bodysites; and controlling the thermal stimulus to increase a blood flow bythe application of the thermal stimulus to the at least two differentbody sites. The controlling of the thermal stimulus comprises forming athermal stimulus pattern formed of a thermal stimulation wave formhaving a peak temperature which heats up a surface of the thermalapplication terminal to be in a range of 40 to 50° C.±5° C. and a heatrelease waveform to stop the heating after the peak temperature isachieved and applying the thermal stimulus pattern in thermalapplication modes comprising an alternative mode or a consecutive modeso as to increase the blood flow at the at least two different bodysites stimulated by 60% to 150% before the thermal stimulation. Theblood flow is measured by a laser Doppler tissue blood flow meterattached to a central part of an inner side of a wrist joint.

In the method for regulating immune cells described above, the specificarea may be at least one area selected from the group consisting of osmetatarsale primam 1 and 2 interosseous, os metatarsale primam 2 and 3interosseous, and part that intersects the perpendicular line of themedial malleolus on an extension line of the medial margin on osmetatarsale primam 1 and 2 in foot sole of right and left.

The two different body sites may include at least one area selected fromthe group consisting of os metatarsale primam 1 and 2 interosseous, osmetatarsale primam 2 and 3 interosseous, and part that intersects theperpendicular line of the medial malleolus on an extension line of themedial margin on os metatarsale primam 1 and 2 in foot sole of right andleft.

BRIEF DESCRIPTION OF THE DRAWINGS

Other features and advantages of the present stimulus method forreleasing stress, and stress-free medical treatment method by thestimulus method will be apparent from the ensuing description, taken inconjunction with the accompanying drawings, in which:

FIG. 1 is a schematic view of an electric type heating apparatus usedfor the present invention;

FIG. 2 is a schematic view of a circuit diagram of an electric typeheating apparatus;

FIG. 3 is a schematic view of a thermal stimulus waveform obtained bycontrolling an electric type heating apparatus;

FIG. 4 is a schematic view of areas of a sole to be stimulated;

FIG. 5 is a schematic view of a protocol of a thermal stimulus;

FIG. 6 is a schematic view of an area near a thyroid gland to bestimulated;

FIG. 7 is a schematic view of an area of a toe of a leg to bestimulated;

FIG. 8 is a diagram illustrating a waveform pattern applied in thethermal stimulus method according to Embodiment 4;

FIG. 9 is a schematic view of an apparatus for applying the thermalstimulus according to one embodiment according to the present invention;

FIGS. 10A and 10B are a table and diagram showing experimental dataobtained by the thermal stimulation method applied to Chu Kyoku Ketsu orpoints according to Embodiment 4;

FIGS. 11A and 11B are a table and diagram showing another experimentaldata obtained by the thermal stimulation method applied to Ken Gu Ketsuor points according to Embodiment 4;

FIGS. 12A and 12B are a table and diagram showing another experimentaldata obtained by the thermal stimulation method applied to Show KaiKetsu or points according to Embodiment 4;

FIGS. 13A and 13B are a table and diagram showing another experimentaldata obtained by the thermal stimulation method applied to Shi In Ketsuor points according to Embodiment 4;

FIGS. 14A and 14B are a table and diagram showing another experimentaldata obtained by the thermal stimulation method applied to Ken ShowKetsu or points according to Embodiment 4;

FIGS. 15A and 15B are a table and diagram showing another experimentaldata obtained by the thermal stimulation method applied to Jin Gei Ketsuor points according to Embodiment 4; and

FIGS. 16A and 16B are a table and diagram showing another experimentaldata obtained by the thermal stimulation method applied to San In KouKetsu or points according to Embodiment 4.

DESCRIPTION

In a stimulus treatment method according to the present invention, astimulus treatment method for providing medical treatment by applying astimulus to a specific area to be stimulated at a body surface by astimulus applying apparatus so as to bring an increase rate of bloodflow to 60% or more, preferably, 100% or more, wherein the blood flow ismeasured by a laser Doppler tissue blood flow meter attached to acentral part of an inner side of a wrist joint.

The specific area is at least one area selected from a group of osmetatarsale primam 1 and 2 interosseous, os metatarsale primam 2 and 3interosseous, and part that intersects the perpendicular line of themedial malleolus on an extension line of the medial margin on osmetatarsale primam 1 and 2 in foot sole of right and left.

The specific area is an area of a near glandula thyreoidea.

The specific area is an area between the outer skin and a horizontalline of the inside boundary part of a hallux distal phalanx bottom and aproximal phalanx bone head in foot sole of right and left.

The stimulus is non-simultaneously and independently applied to at leastone area selected according to a condition of disease.

The stimulus applying apparatus is a heat stimulus applying apparatus,and the heat stimulus applying apparatus forms a warm temperaturestimulus pattern, wherein the stimulus pattern is made up of a thermalstimulus waveform and an interval, and the thermal stimulus waveformincludes a heating waveform obtained by raising temperature to a peaktemperature, 50±5 degrees Celsius by heating, and a heat releasewaveform formed by stopping the heating when the peak temperature isreached.

The stimulus is selected from an acupuncture needle stimulus, a warmtemperature stimulus, an optical stimulus, a magnetic stimulus, and anultrasonic stimulus.

A stress-free treatment method comprises the stimulus method.

An stimulus evaluation method comprises a stimulus method, wherein theincrease rate of the blood flow is used as an indicator of the stimulusevaluation.

In general, two systems will be activated if the stress is applied to aliving organism. One of the systems is a sympathetic nervous systembeginning at a ceruleus nucleus (locus ceruleus), wherein noradrenalinis secreted from nerve ends, and adrenalin is secreted from adrenalcortex.

The other system is a HPA system (hypothalamus*pituitary*adrenal axis),wherein CRH (corticotropine releasing hormone) secreted from ahypothalamus (nucleus paraventricularis) acts on the hypophysis, andACTH (adrenocorticotropic hormone) secreted from the pituitary anteriorlobe (adenohypophysis) acts on the adrenal cortex, whereby finallyglucocorticoid (cortisol) is secreted from the adrenal cortex. Thecortisol is considered as an index of mental/physical stress, and can bealso measured from saliva. In this stimulus, salivary amylase, ACTH, andcortisol were decreased. It would appear that a normalization of astress reaction system hormone takes place.

Cortisol controls carbohydrate, fat, and protein metabolism, and is anindispensable hormone for living organisms. Blood pressure and a bloodsugar level are raised depending on the quantity thereof secreted bystress, and it affects various living organism functions such as animmune system (inflammatory suppression), that is, for example, causinga decline in the immune function, a blood circulatory system, and ametabolism system (sugar rebirth) (glyconeogenesis). Furthermore, thereis a receptor of the cortisol in a hypothalamus, a hippocampus, and ahypophysis, and if the amount of secretion of the cortisol increases,the amount of synthesis of CRH or ACTH decreases. As a result, thecortisol secretion is suppressed. Moreover, in recent years, there havebeen a report, as an index, based on MRI etc. of the brain of a patientwith a PTSD (posttraumatic stress disorder), in which when the cortisolis secreted so much due to excessive stress, it atrophys thehippocampus. Thus, the cortisol also affects a central system(cognition, memory, emotions), and prevention of dementia, etc. can beexpected by using an acupuncture needle stimulus.

A substance, which attracts attention together with the cortisol, isDHEA. The DHEA is a steroid hormone secreted from an adrenal cortex aswell as the cortisol. It has been reported that the action is oppositeto the cortisol. For example, although the cortisol suppresses Th1immunity activity (NK cells, killer T cells) and facilitates Th2immunity activity (B cells), DHEA facilitates the Th1 immunity activityconversely. Moreover, it is thought that patients with depression have ahigh cortisol level and have a low DHEA level, and a ratio thereof(cortisol/DHEA ratio) is important. It is considered that DHEA is ahormone which adjusts an action of the cortisol well.

Moreover, DHEA-sulfate (sulfate group-bound DHEA: DHEAS) (sulfate groupbound form) is also thought to be important. Unlike the cortisol, thereis no negative feedback as to DHEA, and if it is secreted, it is changedinto DHEAS and accumulated, for a comparatively short time. Although theDHEAS itself has no activity as a hormone, the DHEAS is changed intoDHEA in an organ which serves as a target, and acts on the target organ.The DHEAS is considered as an index showing a stable state of the DHEA.The DHEA and DHEAS are considered to have relation with stress.

It is considered that there are mechanism due to vasodilatation andmechanism under influence on sympathetic nerves by such stimulus. Theaction of the dilatation of vessel is considered to increase productionof calcitonin gene-related peptide (CGRP) by the stimulus. It is thoughtthat discharge of the CGRP etc. is increased due to an increase inmuscle blood flow when nerves etc. are stimulated by the stimulus.Namely, efferent autonomic nerves or motor nerves are not included in adorsal spinal nerve root. It is thought that axon-reflex mechanismarises due to a stimulus of afferent nerves etc., and CGRP is dischargedfrom an end thereof, and it is based on the mechanism which a bloodvessel of a governed area is dilated.

Furthermore, the influence on an autonomic nerve activity, which governsa blood vessel, is also assumed. Blood vessels of muscles are governedby adrenergic sympathetic nerves and cholinergic sympathetic nerves. Theformer is vasoconstrictor nerves through an alpha-receptor, and thelatter is vasodilator nerves through acetylcholine. It is said that evenat rest the former always works for the blood vessels of muscle in astate of tonus thereof, so that the blood vessels are always maintainedin a coarctation state to some extent. On the other hand, as to thelatter, it is thought that unstriped muscles of a blood vessel arerelaxed in response to acetylcholine discharged from the end of nerves,so that the blood flow volume increases.

When the stimulus by acupuncture needles or warm temperature heatingmaintains parasympathetic nerve predominance, a long-term sympatheticnerve sthenia status is improved, so that it is also considered thatthere is a possibility that suppression of a RA system in a kidney isfacilitated. This improves a hypertensive patient's QOL.

Furthermore, continuous stimulus treatment such as acupuncture needlesand warm temperature heating showed a tendency of reduced insulin. It isthought that it is based on a continuous improvement of insulinresistance rather than an increase of a temporary insulin secretion.Moreover, obesity is one of the most important risk-factors of IGT.Harris et al. have epidemiologically showed the relation of the IGT andDM, and the obesity, in which that degree of obesity and an increase inweight play a major role in pathogenesis of DM. Therefore, it is thoughtthat an improvement of the obesity problem leads to prevention of DM andalso hypertension. In a medical interview, weight reduction of about 2kg/month on average was confirmed.

Furthermore, in view of a rise in core body temperature and bloodpressure change, etc., it is thought that the stimulus of acupunctureneedles, warm temperature heating, etc. adjusts the blood flow of eachorgan through systemic blood pressure and autonomic nerves. It isthought that there is an effect of acupuncture needles, which areexerted on the systemic blood pressure, that an acupuncture needlestimulus causes a reaction to the systemicity through the sympatheticnerves.

A laser Doppler tissue blood flow meter ALF21D (manufactured by Adovans)is used to measure blood flow on a living tissue. In the laser Dopplertissue blood flow meter ALF21D, when a living tissue is irradiated withsemiconductor laser light (whose wavelength is 780 nm), light reflectedfrom the tissue is converted into an electric signal and the electricsignal is processed, thereby obtaining information of the blood flow.

A C type laser probe (10 mm in diameter, 3 mm in thickness, 2 mm² in alaser irradiation area, and 1 mm in measurement depth) of the laserDoppler tissue blood flow meter was attached to a central part of awrist joint horizontal line, and was measured, taking a 15-minute restafter a stimulus. A warm temperature heating probe is attached betweenbone heads of second and third metacarpal bones. And from measurement ofthe blood flow, an increase rate of the blood flow was calculated.

As to the principle of the laser Doppler tissue blood flow, laser lightcollides with red blood cells, which flow through the inside of a bloodvessel, and the Doppler shift (frequency change), which is produced whenreceiving dispersion, is used. This measurement method is characterizedby non-invasive and real time responsiveness and a capability ofconsecutive measurement. Furthermore, the ALF21D, which was used thistime, could display a blood flow on ml/min/100 g scale. This is becausesignal processing is performed based on the theory of Bonner et al.

Description of the mechanism of an increase in a blood flow in a stressfree treatment will be given below. A mental stress to a living bodystimulates sympathetic nerves through the cerebral limbic system andhypothalamic pituitary, thereby constricting blood vessels and impairingthe microcirculation system including internal organs of the livingbody. In the “stress free treatment” in response to a blood flowreduction response, a rise in body temperature of peripheralsubcutaneous part at distances of 3 mm and 5 mm and, secretion controlof stress hormone (amylase, cortisol, and ACTH) have been confirmed.

Furthermore, Vasoactive Intestinal Peptide (VIP) which is a living bodyactivity hormone accelerates an intestinal peristalsis which is secretedfrom an alimentary canal, a pancreas, and a hypothalamus, and increasesa blood flow including that of the alimentary canal etc. Moreover,vascularization and vascular permeability of microvessel are acceleratedby a vascular endothelial growth factor (VEGF). It is considered thatsince the VIP and VEGF significantly increase by the “stress freetreatment,” both action of the VIP and that of the VEGF were induced, sothat the blood flow of internal organs and peripheral blood flow wereincreased.

From these results, it is considered that with respect to sympatheticnerve activity through the autonomic nerves by the stress stimuli to aliving body and overreaction of hypothalamohypophysial tropic hormones,the “stress free treatment” by thyroid stimulus acts on hypothalamusascendence in an ascending manner, and while discharge of stress hormoneis suppressed, the blood flow was increased through the VIP and VEGF.

Moreover, if a noxious stimulus such as stress and a pain is added to aliving body, a finger tip cutis blood flow decreases, and anasympathetic flow response (SFR) appears. This reaction is evaluated byan index based on a peripheral blood flow as a reaction through asympathetic nervous system against the noxious stimulus. In the stressfree treatment, a blood flow at a central part of a wrist jointhorizontal line increases, according to a laser Doppler tissue bloodflowmeter, and it would appear that a reduction reaction of a bloodflow, which mediates sympathetic flow response (SFR) by stress,increases a blood flow through the VIP and VEGF by the “stress freetreatment” together with the depression effect of stress hormone.

FIG. 1 is a schematic view of an electric type warm temperature heatingapparatus used for the present invention. FIG. 2 is a schematic view ofa circuit diagram of the electric type warm temperature heatingapparatus.

A electric type warm temperature heating apparatus comprises theapparatus 10, and a guide element 14 for a thermal stimulus, which isconnected to the apparatus 10 by a lead 12.

As shown, the apparatus 10 includes a memory unit 16, in which thermalstimulus patterns are stored, a control unit (CPU) 18, which reads out athermal stimulus pattern from the memory unit 16, and an output unit 20,which supplies the thermal stimulus pattern to the guide element 14 fora thermal stimulus. A thermal stimulus is applied to a part to bestimulated, according to the thermal stimulus pattern.

A control unit (CPU) 18 is connected to the memory unit 16. A thermalstimulus pattern for obtaining a stimulus condition equivalent to thatobtained from combustion of moxa is stored in the memory unit 16. Thecontrol unit (CPU) 18 reads out the thermal stimulus pattern from thememory unit 16, controls an output to a heating element(s) based ondetection of a temperature sensor 22, and outputs the thermal stimuluspattern to the guide element(s) for a thermal stimulus.

The apparatus 10 is connected to two or more guide elements for athermal stimulus in order to supply the thermal stimulus pattern to atleast two different areas to be stimulated. In this manner, the thermalstimulus pattern is applied to the areas to be stimulated, through theguide elements for thermal stimulus.

A temperature sensor 22 is provided in a position(s) which is correlatedwith a temperature of an affected area near the heating elements. Theguide elements for a thermal stimulus have a structure set forth below.The guide element 14 for a thermal stimulus, comprises a casing ofapparatus 10, a heater which is provided in the casing, and is used as asource of warm temperature heating for applying thermal stimulus, a heatconduction board, which is provided on a lower face of the casing andwhich conducts heat of the heater to a skin of a patient, and a sealboard provided on an upper face of the casing.

A heat conduction board of the guide elements for a thermal stimuluswhich are placed on two different areas, is desirably made up of atleast two different kinds of metals. In this embodiment, aluminum andsteel are used.

A temperature sensor is provided in a predetermined position of thehousing which is in contact with a part of a human body, and detects thetemperature of the position, so as to send a detection signal to asensor amplifier. The control unit (CPU) controls an output of anelectric power generating circuit so that the temperature of theportion, which is in contact with a skin surface of a human bodycontact, may not exceed a predetermined temperature. In the warmtemperature heating apparatus, the surface temperature of the guideelements for a thermal stimulus is controlled so as to be in a rangefrom 40 to 50±5 degrees Celsius.

When the heating temperature of the heating elements detected by thetemperature sensor is equal to or lower than a reference temperature, apositive side period of a pulse signal is controlled so as to be longand a negative side period of the pulse signal is controlled so as to beshort, according to the output of the temperature sensor. On thecontrary, when it is in a state at the reference temperature, a positiveside period is controlled so as to be short and a negative side periodthereof is controlled so as to be long.

FIG. 3 shows a desirable thermal stimulus waveform, which is obtained bycontrolling the electric type warm temperature heating apparatus. Thethermal stimulus waveform includes a heating waveform 2 obtained byheating it to a predetermined peak temperature, for example, 50±5degrees Celsius, and a heat release waveform 3 which is formed bystopping heating after it reaches the peak temperature.

The heating waveform may be a convex shape heating waveform, an upwardsloping line shape heating waveform, or a concave shape heatingwaveform. Moreover, the heating waveforms are not limited to theabove-described heating waveform. It may be a saw-toothed shapewaveform, and concavo-convex waveform. Moreover, the heating waveformand the heat release waveform may be formed as a sine waveform.

A cycle pattern of a thermal stimulus includes a thermal stimuluswaveform made up of a warm heating waveform and a heat release waveform,and an interval before the next warm heating curve. One cycle pattern ofthe thermal stimulus is desirably set so that a thermal stimulus regionmay be 1 second to 30 seconds and an interval between the heatingregions may be 1 second to 10 seconds.

The pattern of thermal stimulus desirably includes independent thermalstimulus waveforms whose phases are shifted so that the patterns ofthermal stimulus do not substantially overlap each other. That is, asshown in the figures, the pattern of thermal stimulus includes a firstthermal stimulus pattern including an interval between a thermalstimulus region and the next thermal stimulus region, and a secondthermal stimulus pattern, which includes a thermal stimulus regionduring a certain period of an interval of the first thermal stimuluspattern and an interval in a first thermal stimulus region.

A cycle pattern of the thermal stimulus is desirably repeated for 10minutes to 30 minutes. And, the cycle pattern of the thermal stimulus isdesirably repeated again.

In addition, as a stimulus, an optical stimulus, a magnetic stimulus, anultrasonic stimulus, a low frequency wave stimulus etc. may be used inaddition to an acupuncture needle stimulus and a warm temperatureheating stimulus.

Embodiment 1

Subjects were adult men and women. Burn injuries were taken intoconsideration so that an electric type warm temperature heatingapparatus, MXA-8000 (SO-257), was used for a warm temperature heatingstimulus. A probe thereof has a diameter of 10 mm, and a heatingstimulus of warm temperature whose peak is 50±5 degrees Celsius wasintermittently performed for 15 minutes. The probe was attached to thefollowing warm temperature heating to the specific area to be stimulatedof a body surface, and the specific areas was heated at 40 to 50 degreesCelsius.

Here, the specific area to be stimulated is at least one selected from agroup of os metatarsale primam 1 and 2 interosseous, os metatarsaleprimam 2 and 3 interosseous, or part that intersects the perpendicularline of the medial malleolus on an extension line of the medial marginon os metatarsale primam 1 and 2 in foot sole of right and left (referto FIG. 4).

And a warm temperature heating stimulus is desirably applied to at leastone specific area to be stimulated non-simultaneously and independentlydepending on the condition of disease.

Table 1 shows a result of blood flow measured at before and after of thestimulus at a central area of a wrist joint horizontal line by using alaser Doppler tissue blood flow meter, and the increase rate of bloodflow. Wherein a warm temperature heating stimulus is applied at leastone selected from a group of os metatarsale primam 1 and 2 interosseous,os metatarsale primam 2 and 3 interosseous, or part that intersects theperpendicular line of the medial malleolus on an extension line of themedial margin on os metatarsale primam 1 and 2 in foot sole of right andleft as specific area to be stimulated.

TABLE 1 stimulation stimulation increase Patient before after rate No. 11.287 2.1036 63 No. 2 3.2791 8.0098 144 No. 3 1.7603 2.959 68 No. 42.8101 4.6872 68 No. 5 5.9857 13.0065 117 No. 6 3.453 6.9631 102 No. 72.0954 4.7401 126 No. 8 1.4332 3.5227 146 No. 9 1.0091 1.7377 72 No. 103.9592 8.0699 104 No. 11 1.5635 3.8743 148

As shown in the Table 1, the effects of the treatment were remarkablewhen the increase rate of the blood flow was 60% or more, and preferably100% or more. At least one specific area to be stimulated, which aredifferent from each other, are selected. The increase rate of the bloodflow is used as an indicator of the stimulus. The increase rate of theblood flow may be 60% or more, preferably, 100% or more. Also, theincrease rate of the blood flow is used as an indicator in evaluation ofthe stimulus.

Taking into consideration influences on the psychological stress throughautonomic nerves, after keeping the subjects at rest in a state of adorsal position for 20 minutes, the blood pressure, core bodytemperature, salivary amylase, and HEARTRATER (artery age) are measuredand a warm temperature stimulus is performed just for 15 minutes, andthey are measured again immediately after the stimulus.

The protocol of thermal stimulus is shown in FIG. 5. A treatment is madefor the one time and the above-mentioned measurement is carried outbefore and after the treatment and next day thereto. A precapillarycirculation which is innervated by an autonomic nervous system wasmeasured by a deep body thermometer (a deep body temperature monitor,CORE TEMP CM-210 manufactured by TERUMO CORP.), and psychological stressis measured by DAEKI AMY (a salivary amylase monitor manufactured byNIPRO). Furthermore, an arteriosclerosis index and blood vessel age arequantified by HEARTRATER.

Blood is collected twice, that is, before the stimulus and at the sametime one day after the stimulus, and a subject is refrained fromconsuming any food or liquid, except for water after 9:00 PM one daybefore the test and the test day.

Moreover, an advance explanation is made so that they refrain fromundertaking strenuous forms of exercise from 24 hours before the test toone day after the test, and instructions are given to them to use avehicle from home to a laboratory on the morning of the test day ifpossible, and to avoid intense activity and travel with minimum action.

It was observed that temperature rises in the area to be stimulated. Itis noted that an increase in temperature was 2.1, especially when thestimulus was applied to os metatarsale primam 2 and 3 interosseous. Asto salivary amylase, an increase tendency was shown when the stimuluswas applied to os metatarsale primam 2 and 3 interosseous. The salivaryamylase increase +34.25. Moreover, the cortisol is decreased −3.33 at osmetatarsale primam 1 and 2 interosseous, and is decreased −6.33 at partthat intersects the perpendicular line of the medial malleolus on anextension line of the medial margin on os metatarsale primam 1 and 2,

When stimulus was applied to os metatarsale primam 1 and 2 interosseous,a significant decrease of systolic arterial pressure was −13.00.

When a stimulus was applied to os metatarsale primam 1 and 2interosseous, a total cholesterol significantly is decreased −10.33. Theneutral fat also is decreased −24.67 at part that intersects theperpendicular line of the medial malleolus on an extension line of themedial margin on os metatarsale primam 1 and 2. As to A.I.(arteriosclerotic index), when a stimulus was applied to to osmetatarsale primam 1 and 2 interosseous, A.I. is decreased −0.10.

When a stimulus was applied to the area located at os metatarsale primam1 and 2 interosseous; or os metatarsale primam 2 and 3 interosseous, theblood sugar level is decreased by −5.33 or 5.25. Furthermore, ahemoglobin A1c also decreased −0.13, when a stimulus was applied to osmetatarsale primam 2 and 3 interosseous.

The amount of secretion of gastrin which is a gastrointestinal hormonewas significantly increased 19.33 or 48.67, when a stimulus was appliedto an os metatarsale primam 2 and 3 interosseous or part that intersectsthe perpendicular line of the medial malleolus on an extension line ofthe medial margin on an os metatarsale primam 1 and 2. This suggeststhat the digestive absorption and an intestinal peristaltic motion etc.increased.

When a stimulus was applied to an os metatarsale primam 1 and 2interosseous, an Adiponectin is increased +1.5. Since the Adiponectin isconsidered as one of the substances which activates Sirtuin gene, and isone of genes relating to a long life, it was suggested that two stimulito two areas of the plantar part turned ON the gene related to a longlife.

When a stimulus is applied to an os metatarsale primam 1 and 2interosseous, or part that intersects the perpendicular line of themedial malleolus on an extension line of the medial margin on osmetatarsale primam 1 and 2, the leptin is degrease −0.57 or −0.20. Theleptin is called “starvation hormone,” and a body can originally storefat in the body. It is said that at the present day, 95% of cause ofobesity is caused by “leptin resistance” due to excess leptin. It isthought that the Dayez effect would be expected by adjusting the amountof secretion of this substance.

A balance of an autonomic nerve is measured by Heart regulator. A degreeof an activity of an autonomic nerve is increased +28.33 at an osmetatarsale primam 1 and 2 interosseous. A degree of an resistance of anautonomic nerve is increased +14.67 at os metatarsale primam 1 and 2interosseous or +12.25 at os metatarsale primam 2 and 3 interosseous. Anindex of a stress is degreased −17.00 at an os metatarsale primam 1 and2 interosseous. A degree of a fatigue is degreased −30.00 at an osmetatarsale primam 1 and 2 interosseous.

Embodiment 2

In this embodiment, an example which gave the acupuncture needlestimulus was applied to an area near thyroid gland as the specific areato be stimulated (refer to FIG. 6). The thyroid gland is an internalorgan which is located in a shallow position from the body surface, andis observed at the depth in a range of approximately 5 mm-30 mm.Therefore, in general, an examination is performed by using a highfrequency superficial probe in an ultrasonographic examination. The longdiameter of the thyroid gland is approximately 40-50 mm, the thicknessthereof is approximately 12-18 mm, the width diameter thereof isapproximately 15-25 mm, and the thickness of isthmus thereof isapproximately 2-4 mm.

The Acupuncture was performed for a total of ten men and women betweenthe ages of 20 and 60 years old who have diagnosed as high bloodpressure. Expecting influence action to psychological stress which ismediated by autonomic nerves, a disposable acupuncture needle (which wasmade of stainless steel, was 40 mm in length, and was thickness of 0.18mm) was inserted to anterior neck region at a depth of 2-3 cm. Afterkeeping subjects, who were examined, at rest in a state of a dorsalposition for 15 minutes, blood pressure, core body temperature, andsalivary amylase thereof were measured. And then the acupuncture needlestimulus was applied to them for 15 minutes, and they were measuredagain immediately after the needle was got out. The treatment wasperformed seven times, that is, 3 days after the first day, 7 daysthereafter, 10 days thereafter, 14 days thereafter, 17 days thereafter,21 days thereafter,

In EMBODIMENT 2, the blood flow may be measured at before and after ofthe stimulus at a central area of a wrist joint horizontal line by usinga laser Doppler tissue blood flow meter. And the same result as Table 1of EMBODIMENT 1 may be obtained.

Effects

Values of alivary amylase, the highest and the lowest blood pressureshowed significant decreased by the acupuncture needle stimulus. On theother hand, the core body temperatures at distances of 3 mm and 5 mmalso showed the significant rise.

As for the salivary amylase, an increase was observed in +35. It isthought that since there were subjects who always had a highpsychological stress among subjects with hypertension, the removalthereof decreased the pressure. There was a tendency in which systolicarterial pressure and diastolic blood pressure of the subjects decreased−13, when the acupuncture treatment continued. It was observed thatsubjects to whom hypotensor is not administered, rise in blood pressureimmediately after the acupuncture treatment. Subjects, who were low incore body temperature at distances of 3 mm and 5 mm, greatly rose in thedeep core temperature +2, and it was observed that the core bodytemperature converged at normal body temperature on the whole. Moreover,there was a tendency in which core body temperature before theacupuncture treatment became high, when the acupuncture treatmentcontinued.

When the acupuncture treatment continued, the amount of secretion ofcortisol and further that of ACTH which was a higher center thereof,decreased remarkably, immediately after the acupuncture needle treatmentwas performed on zero day, It was observed that it decreased after goingup gently thereafter. Although the cortisol and ACTH of all the subjectstransiently decreased, immediately after the acupuncture needletreatment was performed, and then the gradual increase tendency wasshown, it was observed that there was a tendency in which it decreasedwhen the treatment continued.

It was shown that there was a tendency to gently decrease in T-CHOL,HDL-CHOL, and LDL-CHOL.

Embodiment 3

In this embodiment, moxa cautery was performed on an area between anouter skin and a horizontal line on an inner border part of halluxdistal phalanx bottom of left and/or right foot and phalanx proximalisin foot sole of right and left as a specific area to be stimulated.

In FIG. 7, a symbol “o” shows a specific area to be stimulated betweenthe outer skin and a horizontal line of the inside boundary part of ahallux distal phalanx bottom and a proximal phalanx bone head, andapplies a stimulus.

The moxa was applied to subjects by using pre-rolled moxa. Themoxibustion was continuously performed five times respectively areabetween the outer skin and a horizontal line of the inside boundary partof a hallux distal phalanx bottom and a proximal phalanx bone head, andapplies a stimulus.

The quantity of moxa per one moxibustion is 0.002 g, and the combustiontemperature was 80±5 degrees Celsius at maximum. Two sets of treatments,which were performed in the beginning of week and the end of week, wererepeated three times, that is, the treatment was performed six times intotal.

It was confirmed from clinical data that secretion of thyroid hormonewas activated by applying stimulus to area between the outer skin and ahorizontal line of the inside boundary part of a hallux distal phalanxbottom and a proximal phalanx bone head, and applies a stimulus.

In EMBODIMENT 3, the blood flow may be measured at before and after ofthe stimulus at a central area of a wrist joint horizontal line by usinga laser Doppler tissue blood flow meter. And the same result as Table 1of EMBODIMENT 1 may be obtained.

Thereby, a rise in core body temperature, and prevention and improvementof obesity, diabetes, etc. is achieved. Therefore, it is thought thatthe treatment is one of the effective ways for a therapeutic procedureto lifestyle-related diseases, such as diabetes and obesity. Especially,explanation will be given below with respect to clinical data of a risein core body temperature, diabetes and obesity on which remarkableeffects were shown.

It was performed for a total of nine men and women between the ages of20 and 60 years old who have diagnosed as diabetes, obesity and highblood pressure. Stimulation was applied by moxibustion to parts betweenthe outer skin and the horizontal line of an inner border of halluxdistal phalanx bottom of left and/or right foot and phalanx proximalis.

As described above, there are effects of a rise in core bodytemperature, a reduction of neutral fat, a reduction of cholesterol, areduction of insulin, and suppression of arteriosclerosis.

It is preferred to perform the stimulus treatment to least one of thespecific area to be stimulated selected from a group of EMBODIMENT 1 orEMBODIMENT 2 or

The preceding description has been presented only to illustrate anddescribe exemplary embodiments of the present stimulus method forreleasing stress, and stress-free medical treatment method by thestimulus method. It is not intended to be exhaustive or to limit theinvention to any precise form disclosed. It will be understood by thoseskilled in the art that various changes may be made and equivalents maybe substituted for elements thereof without departing from the scope ofthe invention. In addition, many modifications may be made to adapt aparticular situation or material to the teachings of the inventionwithout departing from the essential scope. Therefore, it is intendedthat the invention not be limited to the particular embodiment disclosedas the best mode contemplated for carrying out this invention, but thatthe invention will include all embodiments falling within the scope ofthe claims. The invention may be practiced otherwise than isspecifically explained and illustrated without departing from its spiritor scope.

Embodiment 4

In another aspect of the present application, the stimulus treatmentdescribed in the present application can be utilized to regulate immunecells. This method can be performed utilizing the apparatus describedabove and illustrated in accompanying drawings.

Treatment to Regulate Immune Cells

The followings are examples of body sites which can be stimulated by thestimulus treatment and results of the stimulations.

-   -   Ken Gu Ketsu or Jianyu points: location) the corner of the        shoulder, the recessed part between the front edge of the outer        periphery of hump and the greater tubercle of humerus.    -   Results; it was observed that T reg. cells in CD4+ T lymphocytes        significantly decrease by about 10%. As shown in FIGS. 11A and        11B, in stimulating Tsu-in, left legs Sanri, and both legs F        points at the same time, the immunity system did not        significantly change. It was observed that in the patients at        the age of 32 or younger, T reg. cells in CD4+ T lymphocytes        decrease. Since the lymphocytes in leucocytes and the T cell        ratio did not vary, it is suggested to be specific to CD4+ T        reg. cells.    -   Jin Gei Ketsu or Renying points: location) the same height as        the regio cervicales anterior and the upper edge of thyroid        cartilage, the front edge of sternocleidomastoid, on the common        carotid artery.    -   Results; it was observed that CD4+ T lymphocytes increase, while        CD8+T lymphocytes decrease and that the CD4/CD8 ratio        significantly increases by 10% or more. As shown in FIGS. 15A        and 15B, since all patients are 30 years old or younger, if the        blood (cardiovascular) system potentially has some problems        resulting from aging, different alterations would be overserved.    -   Show Kai Ketsu or Zhaohai points: location) the margo medialis        pedis, 3.3 cm below the top of Malleolus medialis, the recessed        part below the Malleolus medialis.    -   Results; it was observed that CD4+ T lymphocytes increase, while        CD8+ T reg. cells decrease. As shown in FIGS. 12A and 12B,        regardless of the ages, similar results were observed in all        three patients. It is suggested that among CD4+ T lymphocytes,        cells other than T reg. cells slightly increase.    -   San In Kou or Sanyinjiao points: location) the inside of lower        legs (tibia side), around the back of the inner edge of tibia,        3.3 cm above the top of Malleolus medialis.    -   Results; it was observed that the lymphocytes ratio in        leucocytes significantly decrease by 20% or more. As shown in        FIGS. 16A and 16B, regardless of the ages, similar results were        observed in all three patients. No significant alteration was        observed in T reg. cell ratio in the lymphocytes or CD4+ T        lymphocytes, CD8+ T lymphocyte ratio. It is suggested that        differentiation of all lymphocytes in the bone marrow is        suppressed in relation to the other cells.    -   Shi In Ketsu or Zhiyin points: location) the fifth finger of the        legs, the outer side of distal phalanx.    -   Results; it was observed that CD4+ T lymphocytes slightly        increase, while CD8+T lymphocytes decrease and that CD4+ T reg.        cells significantly increase by 30% or more. As shown in FIGS.        13A and 123B, it was observed that in the patients at the age of        40 or younger, CD4+ T reg. cells tend to remarkably increase.        The increased amount of CD4+ lymphocytes and the increased        amount of CD4+ T reg. cells are similar to each other. It is        suggested that this alteration occurred due to the increase of        CD4+T reg. cells.    -   Ken Show Ketsu or Xuanzhong points: location) the outer side of        lower legs, the front side of fibula, 3.3 cm above the top of        Malleolus lateralis.    -   Results; it was observed that CD4+ T lymphocytes slightly        decrease, while CD8+ T reg. cells decrease. As shown in FIGS.        14A and 14B, similar results were observed in all patients (at        the age of 20 or younger). No alteration in T reg. cells was        observed.    -   Chu Kyoku Ketsu or Zhongji points: location) at the center of        the body.    -   Results; it was observed that CD4+ T lymphocytes slightly        increase, while CD8+ T reg cells decrease and that T reg. cells        significantly increase by 20%. As shown in FIGS. 10A and 10B,        for the patients at the age of 44 or younger, it was observed        that T reg. cells significantly decrease. The data of CD4+ T        reg. cells varied. The decrease of CD8+ lymphocytes and the        decease of T reg. cells correspond to each other. It is        suggested this alteration and variation occurred around CD8+ T        reg. cells.

In this method, the regulation of immune cells can be performed byapplying a stimulus to a specific area to be stimulated at a bodysurface by a stimulus applying apparatus so as to bring an increase rateof blood flow to 60% or more, preferably, 100% or more, wherein theblood flow is measured by a laser Doppler tissue blood flow meterattached to a central part of an inner side of a wrist joint, whereinregulating and balancing these T cell groups finely is essential tomaintain the immune system of human beings and increase in blood flowvolume by thermal therapy enables the “regulatory T cell” (or T-regcell) to regulate and balance the immune cells.

In addition or alternatively, this method may regulate immune cells byperforming the steps of contacting a thermal application terminal withat least two different body sites of the body surface to apply thethermal stimulation to the body sites, controlling the thermalstimulation in a manner that increases the blood flow by the applicationof the thermal stimulation to the body sites, in which the control ofthe thermal stimulation includes forming a thermal stimulation patternwith a thermal stimulation waveform and a heat release waveform. Thethermal stimulation wave form is controlled to have a peak temperaturewhich heats up the surface of the thermal application terminal to be inthe range of 40 degrees Celsius to 50±5 degrees Celsius, and the heatrelease waveform is controlled to stop the heating after the peaktemperature is achieved. The thermal treatment on at least two bodysites with the thermal application terminal can be performed indifferent thermal application modes (operations) which include analternative mode and a consecutive mode, whereby the thermal stimulationcan be controlled to increase the blood flow by 60% to 150% before thetreatment. The blood flow is measured by a laser Doppler tissue bloodflow meter attached to a central part of an inner side of a wrist joint.

In the method for regulating immune cells, the specific area is at leastone area selected from a group of os metatarsale primam 1 and 2interosseous, os metatarsale primam 2 and 3 interosseous, and part thatintersects the perpendicular line of the medial malleolus on anextension line of the medial margin on os metatarsale primam 1 and 2 infoot sole of right and left.

The thermal stimulation method is designed to increase the blood flow,thereby regulating the immune cells effectively. This method ultimatelyprovides health benefits as explained below.

The immune system of human beings cannot function normally without afine balance centering on these T cell groups. A thermal therapyaccording to the present invention reduces stress hormone such ascortisol with 100 percent reproducibility. In addition, immediatelyafter the thermal therapy, two to four times increase in blood flow isprovided.

Simultaneous appearance of VEGF (vascular endothelial growth factor) andVIP (vasoactive intestinal peptide) results in regeneration of innerwalls of a blood vessel, enhancement of blood permeability, andimprovement of blood flow. It is considered that these contributesignificantly to migration property and normalization of immune cells inblood.

The body of a human being constantly fights unlimited variety of foreignfoes such as pathogen, foreign substance, and parasite. A system forprotecting the body against such foreign foes is referred to as“immunity.” The “immune cells” are responsible for the immune system.

The “immune cells” include various types of cells depending on thefunction, such as, detecting a foe invading the body, notifying aninvasion by the foe, directing to start an attack, and signaling startand finish of the attack. Each of them has their own responsibilities,and communicates with each other to work as a team.

Major immune cells are monocyte, lymphocyte (including T cell and Bcell), and granulocyte, which circulates throughout the bloodstream andare collectively referred to as “leukocyte.” If a blood test performedwhile a person has a cold, an inflammation inside the body, or otherdiseases, a high leukocyte count may be observed. This is because immunecells are activated against an abnormality inside the body.

These immune cells maintain the immune function by moving freelythroughout the bloodstream. It is obvious that the sticky blood and badbloodstream reduce each function.

In addition, immune cells communicate with each other and act byreleasing a protein referred to as cytokine. Increased density andviscosity of blood lead to a loss of migration property of theseproteins, and consequently, inherent communicative function is seriouslyimpaired.

Necessity for a Long Life

The human body exists surrounded by foreign substances such as pathogen,harmful chemical substance, virus, and parasite. The human immune systemagainst the foreign substances is a perfect system that ensuresself-tolerance while fighting the foreign substances and foreign foesThus, it can be said that the best thing is to normalize the inherentsystem in human beings.

How Immune Cells are Generated

Leukocyte as well as erythrocyte that delivers oxygen and platelet thatstops bleeding circulate throughout the bloodstream. These are quitedifferent from each other in appearance and function; however, these aregenerated from a common hematopoietic stem cell. A parent cell that canchange to various types of cells is referred to as “stem cell.” Aprocess by which the cell changes from one cell type to another inproperty and function is referred to as “differentiation.” Further, aprocess by which the cell gains specific function to get prepared towork is referred to as “maturation.” The number of hematopoietic stemcells is very small as compared to total number of cells. However,during the course that the stem cells differentiate into immune cells,immune cells proliferate to a large number of immune cells. Thehematopoietic stem cells are found in a liver in fetal life and thenfound in a bone marrow after birth. The hematopoietic stem cells derivedfrom the bone marrow differentiate into “B cell” (an abbreviation forBursa) mainly in gut-associated lymphoid tissue. On the other hand, whenhematopoietic stem cells migrate to thymus above heart, theydifferentiate into T cells. The immune cells thus differentiated fromthe hematopoietic stem cells are delivered to a site where animmunoreaction is generated, such as lymph node and spleen, by theblood, and further differentiate repeatedly to mature into functionalimmune cells. A site where the stem cells first differentiate intoimmune cells, such as bone marrow and thymus, is referred to as “primarylymphoid tissue,” and a site where an immunoreaction is generated isreferred to as “secondary lymphoid tissue.”

Two Trillion Immune Cells Protect the Body

It is said that the number of immune cells in adults is approximatelytwo trillion. The immune cells protect 60 trillion cells in the humanbody. Immune cells circulate throughout the body by the bloodstream, andfight foreign foe with skillful teamwork. A macrophage responds toforeign foe invading the body first. When the macrophage finds a foreignsubstance, it traps expeditiously and engulfs them, and presentsfragment of the foreign substance as an “antigen” to the T cell. T cellsas a commander determine whether the foreign substance is a target foran attack, and then give a command. At first, T cells divide and releasevarious activated molecules. The activated molecules include a factorfor stimulating B cells. On the other hand, B cells recognize antigenswith receptor on their cell surface (immunoglobulin). Subsequently, Bcells initiate a proliferation and a division upon receiving a signalfrom T cells, and differentiate into antibody-producing cells (plasmacells) that generate a large number of antibodies.

In summary, T cells and B cells work in a coordinated manner withrecognizing each other. “To recognize antigens” is a similar manner torecognize a human face by the difference in eyes, a nose, a mouth, andears. Similarly, each antigen has a slightly different size and surface,so B cells recognize the difference. An antibody thus generated canrespond to only one specific antigen. An antibody finds an antigen, andreacts with and binds to it to suppress its action while circulatingthroughout a body by the bloodstream. It is considered that antibodieshave a capability of recognizing as many as 1010 antigens. In fact, thebody of a human being has an immune system that can distinguish morethan 10 billion foreign substances. Immunity fights off antigens by suchexquisite system, and then B cells that have been produced antibodiesdie upon the completion of their role. However, not all B cells die, butsome of the B cells remain in the body as memory B cells. Theseremaining B cells remember the “face” of the antigen firmly to producethe antibody expeditiously in preparation for being invaded by the samefoe again. This is referred to as “immunological memory”. It is saidthat once an individual is affected by “measles,” the individual willnever be affected by the same pathogen, because when the pathogeninvades the body again, memory B cells respond to it expeditiously andproduce a large number of antibodies instantly to kill it.

Tolerant System

Successive attack of immune cells as described above that is initiatedby command and made in succession is strong defense system on highalert. However, the immune system that protects a human body byattacking and eliminating foreign foe must be regulated not to attackthe body's own tissues. This is expressed as “be tolerant to one's self”in the field of immunology. Tolerance is allowance for and acceptance ofothers. That is to say, immunity must be a system which ensures that itdoes not target one's self for attack (=be tolerant to one's self) whileeliminating foreign substances, and thus, discrimination between one'sself and non-self is necessary for the function of this system. This isreferred to as “Immune Tolerance.” A main role in this discrimination isperformed by a T cell. A surface of the T cell has a “T cell antigenreceptor” (TCR: T-cell receptor) for discriminating a large number offoreign foes, which is used to recognize foreign substances. Each T cellhas its own TCR, thereby allowing them to respond to any foreignsubstances expeditiously. This is the identity of T cells that cannot beseen in other types of cells. An antigen receptor TCR can be recombinedin any form. In particular, TCR gene segments are shuffled to createcombinations of TCR in 1010 ways. Such recombination of TCR allows the Tcell to have near infinite discrimination capability. However, a randomcombination also creates cells targeting one's self for attack. Thus, anexquisite system—referred to as negative selection—that eliminates suchharmful cells exists in thymus. In thymus, when an inappropriate orfailed TCR is found, they are destroyed and eliminated instantly. It issaid that 1% or less of T cells are able to pass this strict check.Selecting only harmless T cells not attacking one's self is referred toas “positive selection.” The human body is thereby protected. However,the thymus rapidly degenerates into fat tissue upon reaching adulthood.Therefore, it is believed that autoimmune disease, which one's ownimmune cell attacks the own body, is more likely to be developed.

Types of T Cells

A method for regulating immune cells by increasing blood flow usingthermal therapy according to the present invention is described below indetail. A description for T cells playing a central role in immunefunction is provided below. A T cell that involves in interaction withother immune cells required to produce antibody is referred to as a“helper T cell” (also referred to as CD4-positive T cell). A helper Tcell divides into Th1, Th2, and Th17 that are named based on initials ofT-cell helper, depending on the production pattern of cytokine that is asignal to other cells. A helper T cell also signals to a cell referredto as a “killer T cell” (or “cytotoxic T cell”) that finds and starts adirect attack against foreign substances. On the other hand, a“regulatory T cell” (or T-reg cell) monitors and regulates overallimmunoreaction so as not to overproduce antibodies or not to produceadverse antibodies to one's self. Thus, a regulatory T cell plays animportant role necessary in order for the immunity of the human body tohave tolerance to one's own tissues. In the case of autoimmune diseasein which antibodies attacking one's self are produced, it has beenfrequently reported that the number of regulatory T cells decrease.Whereas, excessive increase in the number of regulatory T cells causesdegradation in function for producing antibodies, and then overallimmunocompetence is weakened. Regulating and balancing these T cellgroups finely is essential to maintain the immune system of humanbeings. Increase in blood flow volume by thermal therapy according tothe present invention enables the “regulatory T cell” (or T-reg cell) toregulate and balance the immune cells.

All Diseases are Autoimmune Disease

Allergies are various adverse effects caused by vital response of immunesystem against foreign substances from outside. It is recognized thatmost of the increasing various diseases including pollinosis, which isalready considered to be national disease, are allergic disease orautoimmune disease. Despite being said that great strides are made inmedical science, the cause of depression and dementia that can be arepresentative example of modern disease remains to be identified, andthe cause of irreversible disorder (disorder from which individualcannot be recovered once it progressed), such as prostatic hyperplasiaand knee osteoarthritis, is also unknown. However, these diseases have acommon factor. The common factor is the presence of debris (=deposit).For example, in the case of Alzheimer's disease that is a representativedisease of dementia, a phenomenon that β amyloid accumulates in thebrain is well known. It is also well known that in the case of kneeosteoarthritis, debris accumulate in joint. It is assumed that similarphenomenon can be observed in prostatic hyperplasia. A decrease in bloodflow underlies the phenomenon. The decrease in blood flow results inpoor circulation, and then generates debris. In the case of kneeosteoarthritis, it is considered that a reduction of synovial fluidderives from the decrease in blood flow. In recent years, it has beenfound that Th17 cells of T cells play a central role in bone destructionof an articular surface that cause an arthrosis. T cells attack one'sown tissues although T cells should be provider of immunity thatprotects the body.

Why does this Happen?

It is considered that the failure of the immune system including the Tcell group due to the decrease in blood flow causes Th17 to attack one'sown tissues. Observation of debris indicates the decrease in blood flow.Thus, when fine balance among T cell groups including helper T cellssuch as Th1 cells, Th2 cells, and Th17 cells, the killer T cell, and theregulatory T cell is lost, immune cells start attacking one's owntissues, that is to say, the autoimmune disease is caused. Furthermore,it is considered that most of diseases are autoimmune disease caused bysimilar processes. In particular, when helper T cells are overactivated,immune tolerance is disrupted and the brunt of an attack is directed toone's own tissues. On the other hand, when regulatory T cells are toopredominant, immunocompetence is weakened, and thereby, onset ofinfection and cancer is triggered. The immune system of human beingscannot function normally without a fine balance centering on these Tcell groups. A thermal therapy according to the present inventionreduces stress hormone such as cortisol with 100 percentreproducibility. In addition, immediately after the thermal therapy, twoto four times increase in blood flow is provided. Simultaneousappearance of VEGF (vascular endothelial growth factor) and VIP(vasoactive intestinal peptide) results in regeneration of inner wallsof a blood vessel, enhancement of blood permeability, and improvement ofblood flow. It is considered that these contribute significantly tomigration property and normalization of immune cells in blood.

In addition, increase in blood flow volume by thermal therapy withelectrical stimulation according to the present invention allowsintentional regulation of increase in volume of an erythrocyte andhemoglobin concentration per an erythrocyte. This increases the watercontent of a cell and normalizes proliferation of a cell. Method forapplying a stimulus to a specific area to be stimulated at a bodysurface by a stimulus applying apparatus so as to bring an increase rateof blood flow to 60% or more, preferably, 100% or more, wherein theblood flow is measured by a laser Doppler tissue blood flow meterattached to a central part of an inner side of a wrist joint isdisclosed at the embodiment described above.

What is claimed is:
 1. A method for regulating immune cells comprising:applying a stimulus to a specific area to be stimulated at a bodysurface by a stimulus applying apparatus so as to bring an increase rateof a blood flow to 60% or more, preferably, 100% or more, wherein theblood flow is measured by a laser Doppler tissue blood flow meterattached to a central part of an inner side of a wrist joint, andwherein regulating and balancing these T cell groups finely is essentialto maintain the immune system of human beings and increase in blood flowvolume by thermal therapy enables a regulatory T cell to regulate andbalance the immune cells.
 2. A method for regulating immune cellscomprising; contacting a thermal application terminal with at least twodifferent body sites of a body surface to apply a thermal stimulus tothe body sites; and controlling the thermal stimulus to increase a bloodflow by the application of the thermal stimulus to the at least twodifferent body sites, wherein the controlling of the thermal stimuluscomprises forming a thermal stimulus pattern formed of a thermalstimulation wave form having a peak temperature which heats up a surfaceof the thermal application terminal to be in a range of 40 to 50° C.±5°C. and a heat release waveform to stop the heating after the peaktemperature is achieved and applying the thermal stimulus pattern inthermal application modes comprising an alternative mode or aconsecutive mode so as to increase the blood flow at the at least twodifferent body sites stimulated by 60% to 150% before the thermalstimulation, and wherein the blood flow is measured by a laser Dopplertissue blood flow meter attached to a central part of an inner side of awrist joint.
 3. The method for regulating immune cells according toclaim 1, wherein the specific area is at least one area selected fromthe group consisting of os metatarsale primam 1 and 2 interosseous, osmetatarsale primam 2 and 3 interosseous, and part that intersects theperpendicular line of the medial malleolus on an extension line of themedial margin on os metatarsale primam 1 and 2 in foot sole of right andleft.
 4. The method for regulating immune cells according to claim 2,wherein the at least two different body sites comprise at least one areaselected from the group consisting of os metatarsale primam 1 and 2interosseous, os metatarsale primam 2 and 3 interosseous, and part thatintersects the perpendicular line of the medial malleolus on anextension line of the medial margin on os metatarsale primam 1 and 2 infoot sole of right and left.